This is a resubmission in response to PAR-10-021 AIDS-Science Track Award for Research Transition (R03) titled Drug Abuse and HIV Adherence Treatments: A Multi-Level, Comparative Meta-Analysis. Substance use and HIV medication adherence problems commonly co-occur and likely mutually impact one another. Though there is a large evidence-based of controlled trials targeting substance use, medication adherence, or both among HIV positive substance users, no secondarily analyses have consolidated the findings. Research synthesis is needed to guide evidence-based practice and inform decision makers on the optimal treatment strategies for HIV positive substance users. The purpose of this project is to use systematic review and meta-analysis methodology to quantify the impact of substance use, medication adherence, and dual focused interventions on both substance use and medication adherence outcomes. We will conduct a comprehensive literature search to identify controlled trials targeting substance use, HIV medication adherence, or both among HIV positive substance users. Coding instruments and a comprehensive coding manual will be developed or modified from previous work to abstract key methodological quality, study design, intervention, and participant characteristics from each study. Trained coders will double rate each included study using the coding instruments. For each study included in the meta-analysis, effect sizes and 95% confidence intervals will be calculated to estimate the magnitude of HIV/AIDS, substance use, and dual focused intervention effect on substance use and medication adherence. Individual studies may contribute one or both of these outcome measures. In addition, several moderator analyses will be conducted to identify factors or subgroups that may impact or moderate the effects of interventions on outcomes. Meta-analysis of well-controlled trials provides the most powerful evidence available for the effects of treatment and is much more accessible and digestible to individual decision makers. The proposed project seeks to shift current research and clinical practice by conducting the first comprehensive meta-analysis on the treatment of HIV infected substance users. PUBLIC HEALTH RELEVANCE: This project will conduct a meta-analysis of interventions targeting HIV medication adherence and/or substance use among HIV positive substance users. Consolidating the research will provide healthcare providers with the information they need to make evidence-based decisions regarding treatment.